Food allergies, of which the first to occur in life is cows' milk allergy, are caused, in most cases, by a reaction to proteins in the food. In the early years of life the immune system is still developing and may fail to develop tolerance to dietary antigens (this may also be described as insufficient induction of oral tolerance). The result is that the baby or child or young animal mounts an exaggerated immune response to the dietary protein and develops an allergic response to it. Food allergies may affect not only humans but also other mammals such as dogs and cats.
Usually, food hypersensitivity develops just after a susceptible baby, child or young animal first encounters a new food containing potential allergens. Apart from its mother's milk, the first dietary proteins generally encountered by human babies at least are cows' milk proteins and, as noted above, cows' milk allergy is the most common food allergy in human babies. It is generally accepted that babies with established cows' milk allergy have an increased risk of developing allergies to other dietary proteins such as egg and cereal proteins. These allergies may manifest themselves clinically as atopic diseases such as atopic dermatitis, eczema and asthma. Even those babies who have successfully developed oral tolerance to cows' milk proteins may subsequently develop allergies to other dietary proteins such as egg and cereal proteins when these are introduced into the diet at weaning.
From a dietary point of view there are only two ways to treat an established allergy—either foods containing the allergen must be avoided altogether, or the foods must be treated to decrease their allergenic potential, for example by extensive hydrolysis. Infant formulas containing extensively hydrolysed cows' milk proteins (peptides consisting of not more than five amino acids) are manufactured for this latter purpose. Similarly it has already been proposed, in U.S. Pat. No. 6,403,142 for example, to prepare petfoods with reduced allergenicity for companion animals where it is suspected that the animal has developed a food allergy. However, exclusion diets have the disadvantages that compliance is low because available foodstuffs are very restricted in the case of avoidance diets and because of poor taste in the case of use of extensively hydrolysed products. Further, there is always a danger that intact allergens will nevertheless be encountered.
Therefore, products have been devised which help to reduce the risk of developing the allergy in the first place, particularly for children thought to be at risk of the same (that is, children having at least one close family member who suffers from an allergy). One example of such products is the infant formulas based on partially hydrolysed whey proteins sold under the trade marks NAN HA1 and NAN HA2. These products have been demonstrated to actively induce oral tolerance to cows' milk proteins. Fritsché et al. (J. Allergy Clin. Immunol, Vol 100, No. 2, pages 266-273, 1997) have shown using animal models that enzymatic hydrolysates of cow's milk proteins with a degree of hydrolysis of 18% were able to induce oral tolerance to intact cow's milk proteins whereas hydrolysates with a degree of hydrolysis of 28% were not. Results of these experiments showed that preventive feeding of rats with such a moderately hydrolysed cow's milk formula, whose allergenicity had been reduced over 100 times as compared to a standard formula, suppressed specific IgE and mediator release from intestinal mast cells, both parameters of an immediate type allergic reaction. This work demonstrated that for cows' milk proteins it is possible to define a degree of enzymatic hydrolysis whereby the capacity of the peptides to induce oral tolerance is maintained whilst their allergenicity is substantially reduced.
Transforming growth factor β, a bioactive peptide found in human milk has been identified as a potential regulator of atopic disease. A meta-analysis has provided evidence for an overall allergy preventing effect of TGF-β in human milk (Gdalevich, 2001). According to Kalliomaki et al (J Allergy Clin. Immunol. 1999 December; 104(6):1251-7), the TGF-beta in colostrum may prevent the development of atopic disease during exclusive breast-feeding and promote specific IgA production in human subjects. Similarly, Oddy et al reported a reduced incidence of wheezing (indicative of respiratory allergy development) in children that had been breast fed for a significant period and had therefore received a high total dose of TGF-β compared to children who had been breast-fed for shorter periods (Oddy et al, J Allergy Clin Immunol). More recently, it has been shown in a rat model that the addition of TGF-β to cows' milk formula reduced allergic sensitisation to cows' milk (Pentilla et al, Pediatr Research 2006).
The period during which young mammals are exclusively milk-fed is relatively short ranging from a few weeks for rats and mice to four to six months for human infants for example. After this period, other foodstuffs containing different dietary proteins are progressively introduced into the diet and the dependence on milk to provide all the nutrients necessary for growth and development is correspondingly reduced in a process commonly called weaning.
Generally, the next dietary protein encountered by young mammals is cereal protein which is introduced at the start of weaning, typically in the form of infant cereals for human infants. Cereal proteins may also provoke allergic reactions when first introduced into the diet of a young mammal even if milk proteins have already been successfully introduced. Thereafter, the young mammal may encounter in rapid succession other dietary proteins including egg, peanut, fish and meat with the risk in each case that an allergic response may result.
However, by comparison with milk proteins, relatively little attention has been paid to the primary prevention of allergic reactions to other dietary proteins such as cereal and egg proteins nor to the possibility of preventing the development of allergic reactions to other antigens such as pollen by means of a dietary intervention. Indeed, this may be an even greater concern given that allergy to cows' milk proteins usually disappears spontaneously between the age of two and five years whereas allergy to cereal and egg proteins for example is generally slower to disappear and may even persist throughout life.
There is, therefore, a need to facilitate the introduction of dietary proteins other than milk proteins into the diet of young mammals at weaning by reducing the risk of development of allergic responses to such proteins as well as a need to reduce the subsequent incidence of atopic diseases whether or not provoked by dietary antigens, particularly in infants at risk of development of allergic responses.